Introducing bubbles to improve cornea reshaping without the creation of a flap

ABSTRACT

Ultra-short pulsed laser radiation is applied to a patient&#39;s eye to create a row of bubbles oriented perpendicular to the axis of vision. The row of bubbles leads to a region of the eye to be ablated. In a second step, a femtosecond laser beam guided through the row of bubbles converts it to a channel perpendicular to the axis of vision. In a third step, a femtosecond laser beam is guided through the channel to ablate a portion of the eye. Using a femtosecond laser with intensity in the range of 1011-1015 W/cm2 for the second and third steps facilitates multi-photon ablation that is practically devoid of eye tissue heating. Creating bubbles in the first step increases the speed of channel creation and channel diameter uniformity, thereby increasing the precision of the subsequent multi-photon ablation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/719,605, filed Dec. 19, 2012, by Nicholas S. Siegele, et al., whichis incorporated by reference as if set forth herein in its entirety.

BACKGROUND

1. Field of the Invention

This invention relates to methods of, and apparatus for eye surgery, andmore particularly to a laser method and apparatus for corneal andintraocular surgery, as well as vision correction.

2. Description of the Related Art

With the development of laser procedures such as LASIK to help correcteye-sight or vision, by reshaping the cornea of the eye, several othernew laser eye-procedures are being considered that concern thephoto-ablation of eye tissue.

U.S. Pat. No. 4,538,608, issued to L'Esperance, Jr. for “Method andApparatus for Removing Cataractous Lens Tissue by Laser Radiation”teaches how to deliver laser energy into the anterior of the eye lensand scan the laser beam in order to photo-ablate cataractous tissue, andhas general importance for the process of photo-ablation of eye tissue,including photo-ablation of stroma. This procedure was improved by J.Bille (U.S. Pat. No. 5,246,435 “Method for Removing CataractousMaterial”), who invented a procedure of laser energy delivery toseparate lamellae in the stroma by focusing a laser beam betweenlamellae layers and photo-ablating tissue at the interface between theselayers.

In those inventions, nanosecond (nsec) type laser beams were considered(for example, 10-20 nsec excimer lasers, or 5-10 nsec Nd/YAG lasers; 1nsec=1×10⁻⁹ sec). With these pulse durations, each laser shot, inaddition to ablating tissue, creates strong shock waves within the eyeand generates significant tissue heating. These effects are undesirable,and may be reduced by using lasers with shorter pulse durations.Therefore, when compact ultra-short lasers, those with pulse durationsless than 1 picosecond (1 psec), [1 psec=10⁻¹² sec], were developed inthe late 1980's, they were considered for use in eye surgery.

In the review article by Christopher Yo et al. on “LASIK, FutureAdvances” (E-Medicine, Nov. 25, 2004) the authors stressed (page 5) that“ . . . one can assume the culprit that negates all the advantages ofcustom ablation may lie in the flap procedure itself. Hence, it would bea great leap in refractive surgery if the LASIK procedure can one day becompleted intrastromally without the need for cutting a flap.” Inaddition, the LASIK flap may lead to complications such as flap striae,epithelial ingrowths beneath the flap, diffuse lamellar keratitis, andflap tears. The present invention responds exactly to the desirableoutcome of corneal refractive surgery without a flap, namely reshapingthe cornea by means of using high intensity femtosecond (fsec) laserpulses for correcting the refractive errors of myopia, hyperopia, andastigmatism without cutting a flap (1 femtosecond=1 fsec=1×10⁻¹⁵ sec).

The general advantage of using fsec lasers for eye surgery compared tousing much longer pulse lasers (nsec-type excimer, Nd/YAG or Nd/Glasslasers) is that with fsec lasers there is a much lower energyrequirement, in particular when the surgery requires eye tissueablation, that is, photo-ablation. Photo-ablation is a thermal processthat requires a certain intensity of laser beam, typically in the rangeof 10⁹-10¹¹ W/cm². For the same ablated spot size, the intensityrequired for photo-ablation is inversely proportional to the pulseduration. For example, laser pulses of 100 fsec duration can providephoto-ablation at hundreds of times smaller beam energies than whenlaser pulses of 10 nsec duration are used. Being able to use smallerbeam energies, ultra-short laser pulses can provide tissue cuts withless eye trauma, as was proven experimentally. This observation leads tothree principal advantages of using ultra-short laser pulses for eyesurgery. One advantage is that it is possible to perform much higherprecision tissue cuts with such lasers when compared withnanosecond-type lasers. A second advantage is that ultra-short laserpulses produce much smaller heating effects in tissue when compared withlonger laser pulses, greatly reducing tissue damage. A third advantageis that ultra-short laser pulses produce only very weak shock waves intissue, whereas long laser pulses produce very substantial shock wavesresulting in considerable trauma. In eye surgery, this trauma can havesubstantial negative effects on the prognosis following surgery, such asinflammation and undesirable wound healing.

In addition to photo-ablation, laser pulses can be used to producephoto-disruption, which is also a thermal process. The photo-disruptionprocess can result in the formation of bubbles, i.e. cavity bubbles orgas bubbles in the tissue. This requires significantly less intensitythan photo-ablation, typically in the range of 10⁸-10⁹ W/cm².

In conventional LASIK procedures, where a flap is created by using amechanical microkeratome, photo-disruption provides the basis forreplacing the mechanical flap cut with a much more precise flap cutusing a fsec laser [Juhasz et al., U.S. Pat. No. 5,993,438 (issued Nov.30, 1999) “Intrastromal photorefractive keratectomy”, T. Juhasz, U.S.Pat. No. 6,110,116 (issued Aug. 29, 2000) “Method for corneal lasersurgery”, and T. Juhasz et al., U.S. Pat. No. 6,146,375 (issued Nov. 14,2000) “Device and method for internal surface sclerostomy”]. U.S. Pat.No. 6,146,375 also teaches about using fsec or picosecond (psec) pulsesfor the treatment of glaucoma. T. Juhasz et al.'s research has led tothe successful company “IntraLase” that markets the procedure forcutting the flap with a fsec laser in preparation for LASIK eye surgery,where the corneal correction itself uses an excimer laser providingpulses of 10-20 nsec duration.

In The patent application “Method and Device for Corneal Reshaping byIntrastromal Tissue Removal” by S. Suckewer, P. Hersh, A. Smits, and A.Morozov, published by US Patent Office on Feb. 28, 2008 (Pub. No: US2008/0051772 A1) a new approach to cornea reshaping is described. Thisinvention teaches how to apply a laser beam to reshape the eye's corneaunder the cornea's surface without creating or removing a flap, hence itis called Flapless LASIK.

Flapless LASIK is a two-step procedure. The first step creates long andnarrow channels in the cornea with a laser beam oriented approximatelyperpendicular to the axis of vision. Such channels lead to the regionsthat are to be ablated. In the second step, the fsec laser beam, throughsuch channels, reaches the stroma between the inner (endothelial) andouter (superficial) cornea and results in ablation of the stroma at aspot. By changing the position of the focusing lens or focusing mirror,the location of the ablation spot moves along the channel. Controllingthe number of laser pulses for each spot controls the amount of ablatedmaterial in each spot. The preferred laser beams consist of ultra-shortpulses of duration 30-200 fsec, although the duration could be shorteror longer, at repetition rates of 1,000-10,000 Hz, with higher or lowerrepetition rates possible as well, and intensity in the range of10¹³-10¹⁵ watts/cm², resulting in what the inventors termed“multi-photon ablation”.

SUMMARY OF THE INVENTION

The present invention relates to improving the Flapless LASIK method byadding an additional initial step prior to creating the channel bycreating bubbles by photo-disruption under the surface of the cornea inorder to increase the speed of the laser beam penetrating into the areaof corneal ablation. In a preferred embodiment, this improved FlaplessLASIK may be is a three-step procedure. The additional first step usespreferably an fsec laser beam that is typically oriented parallel to theaxis of vision to create, via photo-disruption, one or more long andnarrow rows of bubbles in the cornea that are oriented approximatelyperpendicular, or at a greater or lesser angle, to the axis of vision.Such bubble rows lead to the regions that are to be ablated.

In the next step, the fsec laser beam of much higher intensity than thelaser beam applied for the first step, through such bubble rows, reachesthe stroma between the inner (endothelial) and outer (superficial)cornea, creating a channel using multi-photon ablation. In the nextstep, the fsec beam, after reaching the stroma, ablates the stroma at aspot using multi-photon ablation. By changing the position of thefocusing lens or focusing minor, the location of the ablation spot canmoves along the channel. Because it may be is preferable to use minimumpulse energy, hence minimum pulse intensity, to create the channel bymulti-photon ablation in order to keep the channel at a relatively smalldiameter, it may be desirable to increase the laser pulse energy and itsintensity in this said third step. This can easily be accomplished bychanging the voltage on the power supply to the laser amplifier or byincreasing the diaphragm that limits the laser beam's diameter.Moreover, controlling the number of laser pulses for each spot is amethod to controls the amount of ablated material in each spot.

The bubbles created in the first step may not only increase the speed ofthe ablation channel's creation in the cornea, thus increasing the rateof ablation, but also may make the diameter of such channels moreuniform, hence decreasing energy losses of high intensity fsec laserpulses during their propagation through the channels and improving theprecision of the stromal ablation.

In the present invention the fsec laser beam is divided into 2 beams,although a single beam at any given time or two or more separate laserbeam sources could be used. The first beam, which may be of very lowpulse energy in the a range of 1 to 10 micro-Joule (μJ), which could behigher or lower, and intensity in the range 10⁸ to 10⁹ W/cm², whichcould be higher or lower, can be is delivered to the eye approximatelyalong the vision axis, hence approximately perpendicular to the secondlaser beam, to create at least one line of bubbles that runapproximately perpendicular to the axis of sight. The second beam thencreates a channel through the bubble row or rows by means ofmulti-photon ablation, and after reaching the end of the channel or theablation target, ablates the chosen areas also using multi-photonablation.

The first beam creates bubbles at depths of 150-250 μm below the surfaceof the cornea, although it could be shallower or deeper, along anapproximately straight line as a precursor for the channel. The bubblesare created using photo-disruption and their creation does not damagethe cornea. Bubbles are typically created in one to two rows, but therecan be more rows, next to each other on a plane approximately parallelto the surface of the cornea. In addition to this method for creatingthe bubble row(s), a cylindrical lens can be implemented with thefemtosecond laser oriented approximately parallel to the axis of vision,which creates one row of bubbles per pulse from the fsec laser. Thus oneor more rows of bubbles can be created, stretching from the edge of theeye's cornea to the point of ablation in the stroma, in a very shortperiod of time, whereas the main ablation beam then passes throughbetween approximately tens of nanoseconds and tens of microsecondslater.

The present invention, improved Flapless LASIK, has been demonstrated onfresh pig eyes from an eye bank. Using a 50 fsec or 100 fsec,approximately from 1 to 10 μJ laser beam, which was tightly focused witha short focal length lens down to a range of 30 to 100 μm diameter on aplane approximately parallel to the cornea's surface, one, two or eventhree rows of bubbles were created. The focused fsec or psec laser beamspot moved along the stroma, at a speed of approximately 0.25 mm/s orfaster, to form a bubble region. Introducing the laser ablation beaminto the row(s) of bubbles, the speed of creation of a 3 mm channel fromthe edge of the cornea to the area required for ablation was 1.5-2 timesfaster than without bubbles, all other conditions being the same in bothcases. This idea, of course, can be applied to two or more laserablating beams.

The importance of this invention is three-fold, namely it improves theuniformity of the channels leading to lower losses of energy of laserbeams during their propagation through the channels, decreases the timeof the stroma ablation procedure, and improves the precision of saidstroma ablation.

Various implements are known in the art, but fail to address all of theproblems solved by the invention described herein. Various embodimentsof this invention are illustrated in the accompanying drawings and willbe described in more detail herein below.

BRIEF DESCRIPTION OF THE DRAWINGS

Other objects and advantages of the invention may become apparent uponreading the following detailed description and upon reference to theaccompanying drawings.

FIG. 1 shows a schematic side view of prior art cornea laser ablationafter creating a flap.

FIG. 2 shows a schematic side view of creating a row of bubbles by laserinduced photo-disruption, a step in a process for removing material froman interior portion of a cornea of the present invention.

FIG. 3 shows a schematic side view of creating a row of bubbles by laserinduced photo-disruption using a cylindrical lens.

FIG. 4 shows a schematic side view of creating a row of bubbles by laserinduced photo-disruption using a combination of a spherical lens and acylindrical lens.

FIG. 5 shows a schematic side view of converting a row of bubbles into amicro-channel by laser induced ablation or multi-photon ablation,another step in a process for removing material from an interior portionof a cornea of the present invention.

FIG. 6 shows a schematic side view of creating a void within an interiorportion of a cornea by removing material using laser inducedmulti-photon ablation enabled by a laser directed down the temporarymicro-channel, yet another step in a process for removing material froman interior portion of a cornea of the present invention.

FIG. 7 shows a schematic plan view of creating a void within an interiorportion of a cornea by removing material using laser inducedmulti-photon ablation enabled by a laser directed down the temporarymicro-channel.

While the invention is subject to various modifications and alternativeforms, specific embodiments thereof are shown by way of example in thedrawings and the accompanying detailed description. It should beunderstood, however, that the drawings and detailed description are notintended to limit the invention to the particular embodiment which isdescribed. This disclosure is instead intended to cover allmodifications, equivalents and alternatives falling within the scope ofthe present invention as defined by the appended claims. Further, thedrawings may not be to scale, and may exaggerate one or more componentsin order to facilitate an understanding of the various featuresdescribed herein.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

One or more embodiments of the invention are described below. It shouldbe noted that these and any other embodiments described below areexemplary and are intended to be illustrative of the invention ratherthan limiting.

The preferred embodiments of the present invention will now be describedwith reference to the drawings. Identical elements in the variousfigures are identified with the same reference numerals.

Reference will now be made in detail to embodiments of the presentinvention. Such embodiments are provided by way of explanation of thepresent invention, which is not intended to be limited thereto. In fact,those of ordinary skill in the art may appreciate upon reading thepresent specification and viewing the present drawings that variousmodifications and variations can be made thereto.

FIG. 1 shows a schematic side view of prior art cornea LASIK laserablation after creating a flap. With the flap 105 lifted aside, a laserbeam 115 may ablate the interior of the cornea 110 directly, removingmaterial from an ablated area 130 by photo-ablation, a heat mediatedprocess. In such surgery, the laser beam 115 may be directedsubstantially along the optical axis, a.k.a. the axis of vision 125.

The present invention improves on both the LASIK, and the prior FlaplessLASIK method by, as an initial step, creating bubbles under the surfaceof the cornea in order to increase the speed of the laser beampenetrating into the area of corneal ablation. This improved FlaplessLASIK procedure is a three-step procedure.

In the first step, shown in FIG. 2, a laser beam oriented near parallel,or at a greater angle, to the axis of vision creates one or more longand narrow rows of bubbles in the cornea of the eye. Such a bubble rowor rows may lead to the regions that are to be ablated in subsequentsteps.

In the second step, shown in FIG. 5, a femtosecond laser beam, directedthrough such bubble rows, reaches the stroma, between the inner(endothelial) and outer (superficial) cornea, creating a channel that isabout perpendicular to the axis of vision or at a lesser or greaterangle.

In the third step, shown in FIG. 6, a femtosecond laser beam, afterreaching the stroma, ablates the stroma at targeted spots.

While the present invention is directed toward creating a channel withinthe cornea to reach the stroma, it can be applied to other areas of theeye.

The steps of bubble creation, channel creation, and ablation of materialcan be accomplished by using one, two or three laser beams, whereby oneor more laser sources may be used to generate the laser beams. Forinstance, a single laser source can be used that generates a singlelaser beam, preferably a femtosecond laser beam, that is divided intotwo beams, where the first beam performs the bubble creation and thesecond beam creates the channel and then ablates the target material. Asecond alternative would utilize two separate laser sources, where thefirst source generates the laser beam that creates the bubbles and thesecond source generates the laser beam that creates the channel and thenablates the target material. A third alternative would utilize a singlelaser source that emits a single laser beam at any given time andwithout splitting the beam, whereby the beam would initially be directedto create the bubbles, and once the bubbles were complete, the beamwould be directed to create the channel and then ablate the material. Afourth alternative would utilize three separate laser beams, that wouldemit from one, two or three laser sources, whereby the first laser beamcreates the bubbles, the second laser beam creates the channel, and thethird laser beam ablates the target material.

The preferred laser beams consist of pulses in the range of 30 to 200fsec duration, which could be longer or shorter, at repetition rates of100 to 10,000 Hz, which could be higher or lower, and with varyingintensities depending on the process or step being undertaken.

The First Step

In this initial step, shown in FIG. 2, a laser beam 115 of very lowpulse energy, preferably in the range of 1 to 10 μA, though it may, withdiminishing efficacy, be higher or lower, and with a focused intensitythat is preferably in the range of 10⁸-10⁹ W/cm², may be used. Any othersuch parameters that are sufficient to initiate a photo-disruptionprocess may also be used, but may have significantly diminishedefficacy. In one embodiment, a plurality of ultra-short laser pulses 115are delivered to the eye approximately along, or parallel to, the visionaxis 170, hence approximately perpendicular to the second laser beamused in the later steps shown in FIGS. 4 and 5. The laser may also bedirected at different angles to the vision axis, though other anglestend to require more complex optical arrangements to achieveconsistently good results. These pulsed may be used to create at leastone row of bubbles 155 at depths of 150-250 μm below the surface of thecornea, although it could be shallower or deeper, that creates a stringor row of bubbles, which may be created in an approximately straightline. A femtosecond or picosecond laser could be used to create thebubbles. This line of bubbles 155 is a precursor for the channel that iscreated in the second step.

FIG. 2 shows a schematic side view of this step of creating a row ofbubbles 155 by laser induced photo-disruption. As seen in FIG. 2, alaser amplifier and power supply 140 may be interfaced to programmablecontrol circuitry 145, and may be used to generate a pulsed laser beam115 that may be focused down to produce a pulse intensity in a range of10⁸ to 10⁹ W/cm² within a vicinity of the focal point. The laser beam115 may, for instance, be focused by optical elements 150 such as, butnot limited to, concave and convex spherical lenses, cylindrical lenses,prisms, beam-splitters, adjustable diaphragms, minors or somecombination thereof. A bubble formed by photo-disruption 155 may besimilar in diameter to the focus diameter 220 of the laser pulse, i.e.,in a range from 10 μm to 100 μm. While creating the row of bubbles 135,the laser beam 115 may be directed substantially parallel to the opticalaxis, a.k.a. the axis of vision 125, thought the row of bubbles 135 maylie substantially perpendicular to this axis. This may be achieved by,for instance, by translating the optical elements 150 perpendicular tothe axis of vision 125 in small incremental steps by means of amicro-transducer such as, but not limited to, a piezo-electric drive, astepper motor controlled micrometer thread, or some combination thereof,all of which may be manipulated via the control circuitry 145. The rowof bubbles may also be created by related methods such as, but notlimited to, tilting the optics, using one or more steering mirrors, orsome combination thereof.

The bubbles are created using photo-disruption and their creation doesnot damage the cornea, and in particular does not damage the thin areaof cornea corresponding to the flap area of regular LASIK. The bubblesare created in the range of between tens of nanoseconds [1 nanosecond (1nsec)=10⁻⁹ sec] and tens of microseconds [1 microsecond (1 μsec)=10⁻⁶sec] before the main ablation channel is created, although that timespan could be shorter or longer. Bubbles are typically created in one totwo rows, but there can be more rows, next to each other on a planeapproximately parallel to the surface of the cornea. The focused laserbeam spot may be moved along the stroma, at a speed of approximately0.25 mm/s or faster, to form a bubble region.

In another embodiment of creating the bubble row or rows, shown in FIG.3, a cylindrical lens 215 can be implemented with the laser 140 orientedapproximately parallel to the axis of vision 125, which creates one rowof bubbles 135 per single pulse from the laser. Thus one or more rows ofbubbles can be created, stretching from the edge of the eye's cornea tothe point of ablation in the stroma, in a shorter period of time thanwithout the use of a cylindrical lens.

FIG. 3 shows a schematic side view of creating a row of bubbles by laserinduced photo-disruption using a cylindrical lens 215. The laseramplifier and power supply 140 overseen by control circuitry 145 maygenerate a suitably shaped and powered beam that may be focused by thecylindrical lens 215 to form a focal line 225. The focal line may createthe row of bubbles 135 in a single step, or may be stepped perpendicularto the axis of vision 125, creating the row of bubbles 135 in two ormore steps. Using a focal line may increase the speed of the rowcreating process, but may require a higher powered laser to produce therequired focused intensity to produce photo-disruption.

In another embodiment, a laser beam oriented approximately perpendicularto the axis of sight can sequentially create bubbles at varying depths,thereby creating a bubble row or rows.

In the event that the creation of the bubble row 135 or rows requires ashorter channel length without losing laser beam energy, an additionalspherical lens can be applied. Such lens, with a diameter that can beapproximately equal to the length of the cylindrical lens, is placedjust above or below the cylindrical lens. The combination of theselenses both placed in the path of the laser beam can change theelongation of the laser beam to better match a distance from theentrance of the ablation laser beam into the cornea up to the desiredarea of stromal ablation.

FIG. 4 shows a schematic side view of creating a row of bubbles by laserinduced photo-disruption using a combination of one or more sphericallenses 210 and a cylindrical lens 215. The spherical lenses 210 may, forinstance, act as beam shaping elements that may optimize the beam shapeso that the spherical lens 210 may create a focal line 225 optimized forcreating the row of bubbles 135 by photo-disruption.

In another embodiment, more than one bubble row may be createdapproximately parallel to one another in order to create a widerdiameter channel. This may provide improved control of the channel'sperpendicular size as well as a channel with improved uniformity,compared to a channel of the same diameter that is created using asingle row of bubbles. The resulting channel may be ellipsoidal in shapewith a width in the range of 50 to 100 μm, which may be smaller orgreater.

While the focus size of a cylindrical lens d_(cyl) without the use of aspherical lens may be in the range of 10 to 100 μm and elongated alongthe cylindrical lens axis, for example ζ_(cyl)=5 mm, using a cylindricallens in conjunction with a spherical lens of long focal length, hencelarge focal spot diameter, for example d=2 mm, will produce a focal spotlength ζ_(cyl−d)=2 mm practically without significant change ofd_(cyl−d)≈d_(cyl).

The Second Step

In the second step, as shown in FIG. 5, a laser beam 190 creates thechannel 180 by means of multi-photon ablation through the row or rows ofbubbles by connecting by multi-photon ablation said row or rows ofbubbles, where the channel typically extends from an outer (superficial)surface of the cornea 110 to a channel end point 185 located within saidcornea (the endothelial cornea). The channel allows for ablation orremoval of material at the channel end point as well as along thechannel.

This channel creating laser beam has a preferred pulse energy range of0.1 mJ to 1 mJ and a focus diameter range of 10 μm to 100 μm, althougheach of these variables could be less than or greater than specifiedherein. The channel is created using multi-photon ablation, whichrequires a pulse intensity of 1012 watts/cm² or greater, although apulse intensity in the range of 1013-1015 W/cm² is preferred. As thepulse intensity increases, the probability of initiating multi-photonablation on a given pulse increases. However, higher energies willcreate wider channels, which may be less desirable. Use of lower pulseintensity that creates the channel via photo-ablation is possible, butthis would result in thermal damage that would cause a longer channelclosure and a longer healing time.

The Third Step

Once the channel is created, the energy level of the laser beam may bekept constant or it may be increased, preferably by a factor of from 2to 5 in comparison to the laser pulse energy for creation of thechannel, or a different laser beam may be used at such energy levels.The pulse intensity is preferably increased to or maintained in therange of 10¹³-10¹⁵ W/cm², and by focusing the laser at targeted tissue,the tissue is removed by multi-photon ablation. Keeping the energy ofeach laser pulse at approximately a constant value for the given pulseduration and the focal spot size is important to reach and maintain theapproximately constant intensity for multi-photon ablation of livetissue. The channel may, for instance, also provide a means of removalof the ablated material in the form of a gas or a liquid, or acombination thereof. The removal of the ablated material may, forinstance, occur as the result of a pressure differential between thevoid and the ambient room pressure. The procedure may, for instance, beconducted in a reduced pressure environment to provide improved removalof the ablated material. A separate channel or channels mayalternatively be provided for the removal of the ablated material.

FIG. 6 shows a schematic side view of this step of creating a void 195within an interior portion of the cornea 110 by removing material usinglaser induced multi-photon ablation enabled by laser beam consisting ofa second plurality of ultra-short laser pulses 205 directed down thetemporary micro-channel 180. The laser amplifier and power supply 140,under control of programmable circuitry 145, may, for instance, producespulses having energies in a range of 0.1 mJ to 5 mJ. These pulses may befocused down by optical elements 150 to produce pulse intensities in arange of 10¹² to 10¹⁵ W/cm². These high intensity pulses may inducemulti-photon ablation within the temporary micro-channel 180 or in avicinity of the micro-channel end point 185.

By changing the position of the focusing lens or focusing minor, thelocation of the ablation spot can be moved along the channel.Controlling the number of laser pulses for each spot controls the amountof ablated material in each spot. By increasing the number of laserpulses more material will be ablated per unit of time, and by decreasingthe number of laser pulses less material will be ablated per unit oftime.

By maintaining the pulse repetition rate, preferably in the range of 1kHz or greater during this third step, the channel opening can becontrolled or maintained until the desired ablations and procedures canbe completed. Once the procedures are complete, the channel willspontaneously close and heal within several minutes, most of the time inless than 3 minutes, whereby smaller diameter channels may heal fasterthan larger diameter channels.

Multi-Photon Ablation

The second and third steps are preferably accomplished using“multi-photon ablation”. Multi-photon ablation is a completely differentmethod of material removal than photo-ablation. Multi-photon ablationrequires a high laser pulse intensity, equal to or higher than 10¹²W/cm² and preferably in the range of 10¹³-10¹⁵ W/cm², in order to removeparticles, i.e. molecules and atoms, from targets. Multi-photon ablationoperates by means of instantaneous absorption of several photons, fasterthan the molecule's or atom's relaxation time, and creates an ultra-highelectric field in the vicinity of such particles. This causes anon-thermal ablation of matter, whereas other laser based ablationmethods are thermal.

For example, a 5 mJ pulse with 50 femtosecond pulse duration focuseddown to a diameter of 10 to 100 μm provides a pulse intensity in therange of 10¹³-10¹⁵ W/cm². At such intensities particles (molecules,atoms) at the surface of the target material, for instance tissue, areunder a very high electric field, which may exceed the work force, orbounding, of a molecule or atom to the target such as tissue material,therefore freeing them from the target surface and creating the effectof ablation but practically without heating the target material.

Initiating multi-photon ablation with a given laser pulse is based onprobability that is most affected by the pulse intensity. So, whilemulti-photon ablation may be possible below an intensity of 10¹² W/cm²,the probability that a given pulse causes multi-photon ablation at lowerintensities is significantly lower. As such, descriptions herein ofmulti-photon ablation processes do not preclude the possibility thatcertain laser pulses within such processes will fail to invokemulti-photon ablation and that certain pulses may thereby invokephoto-ablation.

FIG. 7 shows a schematic plan view of creating a void 195 within aninterior portion of a cornea 110 by removing material using laserinduced multi-photon ablation enabled by a laser 140 directed down thetemporary micro-channel 180.

Benefits of Bubble Creation

The second and third steps can alternatively be performed as describedwithout initially performing the first step of bubble creation. However,creating the bubbles prior to creating the channel provides severalbenefits in addition to those benefits provided in creating the channelwithout first creating the bubbles. First, implementing the bubblecreation step increases the speed of the ablation channel's creation inthe cornea. For example, the speed of creation of a 3 mm channel fromthe edge of the cornea to the area required for ablation was 1.5-2 timesfaster than without bubbles, all other conditions being the same.Second, the bubble creation provides for a more uniform channeldiameter, which significantly increases the uniformity of the laser beamfrom shot-to-shot while traveling to the spot of ablation, improving theprecision of the ablation. As seen from comparing the ablation timesbetween ablation of material where the channel was created with andwithout the initial bubble creation step, this increased channeluniformity decreases losses of energy of the laser pulses, which allowsfor the effective and practical use of a lower level of pulse intensityfor the multi-photon ablation of target materials by as much as about anorder of magnitude.

Other Applications

While the procedures disclosed herein are described as they apply to theeye, they may alternatively be applied to create channels in material ororganic tissue, for example whereby the bubbles are initially created inthe organic tissue using photo-disruption, fsec laser pulses then createthe channel through the bubbles using multi-photon ablation, and ifablation is desired fsec laser pulses ablate matter using multi-photonablation or other ablation techniques.

Additionally, once a channel is created via steps 1 and 2, or via step2, described herein, procedures other than ablation may be implementedthrough the channel, or material, drugs, or devices may be insertedthrough the channel.

Although this invention has been described with a certain degree ofparticularity, it is to be understood that the present disclosure hasbeen made only by way of illustration and that numerous changes in thedetails of construction and arrangement of parts may be resorted towithout departing from the spirit and the scope of the invention.

What is claimed is:
 1. A method of removing material from an internal portion of an eye comprising: creating a first row of bubbles below the surface of the eye with a first laser beam, wherein all of said bubbles in said first row of bubbles are linearly aligned; creating a channel through the linearly aligned first row of bubbles with a second laser beam; and multi-photon ablating material located along or at the end of said channel with said second laser beam.
 2. The method of claim 1 wherein said channel is created from 10⁻⁹ seconds to 10⁻⁶ seconds after said first row of bubbles is created.
 3. The method of claim 2 wherein said first laser beam creating said first row of bubbles has a pulse intensity of from 10⁸ to 10⁹ W/cm²; said second laser beam creating said channel through said first row of bubbles has a pulse intensity of from 10¹¹ to 10¹⁵ W/cm²; and said second laser beam ablating the material has a pulse intensity from 10¹² to 10¹⁵ W/cm².
 4. The method of claim 3 wherein said first laser beam creating said first row of bubbles has a pulse energy of from 1 to 10 μJ; said second laser beam creating said channel through said first row of bubbles has a pulse energy of from 0.1 mJ to 1 mJ; and said second laser beam ablating the material has an energy level from 0.1 mJ to 5 mJ.
 5. The method of claim 4 wherein said second laser beam creating said channel through said first row of bubbles has a focus diameter from 10 μm to 100 μm.
 6. The method of claim 4 wherein said multi-photon ablation of material is conducted with pulses having a repetition rate of 1 KHz or greater.
 7. The method of claim 4 wherein pulses of said first laser beam that creates a first row of bubbles below the surface of the eye are delivered along the axis of vision; and wherein said first row of bubbles are created perpendicular to the axis of vision.
 8. The method of claim 4 wherein said first row of bubbles are created at a depth from 150 μm to 250 μm below the surface of the eye's cornea.
 9. The method of claim 4 wherein the pulses of said second laser beam has a duration from 30 to 200 fsec.
 10. The method of claim 4 wherein the pulses of said second laser beam has a repetition rate from 100 to 10,000 Hz.
 11. The method of claim 4 wherein a single initial laser beam is divided to create said first laser beam that creates said first row of bubbles and said second laser beam that creates said channel and ablates said material.
 12. The method of claim 4 wherein more than one row of bubbles are created, and said creation of the channel is through more than one row of bubbles.
 13. The method of claim 2 wherein said channel extends from an outer surface of the eye's cornea to an end point within the eye's cornea.
 14. The method of claim 2 wherein said material that is ablated consists of at least a portion of the eye's stroma.
 15. The method of claim 14 wherein said ablation of the stroma improves the refractive properties of the eye's cornea.
 16. The method of claim 2: wherein the row of bubbles is created below the surface of the eye's cornea; wherein creating the channel through the row of bubbles with said second laser beam comprises creating a temporary micro-channel extending from a surface of said cornea to a micro-channel end point located within said cornea by delivering a first plurality of ultra-short laser pulses through said row of bubbles; and wherein ablating said material located along or at the end of said channel with said second laser beam comprises delivering a second plurality of ultra-short laser pulses with pulse energies of 20 μJ or greater and focused down to a pulse intensity in a range of 10¹² to 10¹⁵ W/cm² and thereby generating a void. 